1. Field of the Invention
This invention relates to various decahydro-8H-isoquino[2,1-g][1,6]-naphthyridine and decahydrobenzo[a]pyrrolo[2,3-e]quinolizine derivatives, the compounds of formula (I), and pharmaceutically acceptable salts thereof, which exhibit useful pharmacological properties, including selective .alpha..sub.2 -adrenoceptor antagonist properties and 5-HT.sub.1A receptor partial agonist properties.
Selective .alpha..sub.2 -adrenoceptor antagonists are known to block the effects of adrenaline and noradrenaline on the noradrenergic system in mammals, causing many different results, including increased noradrenaline release from noradrenergic nerve endings. Such a result has been found to be beneficial in the treatment of disease states such as depression, impotence, sexual dysfunction, and for a variety of vascular disorders (see, for example, McGrath, Brown and Wilson, Med. Res. Rev., Vol. 9, pp. 407-533 (1989)).
Partial agonists of 5-HT.sub.1A (5-hydroxytryptamine) receptors modify serotonergic function in mammals, and have been found to be useful in the treatment of disorders such as anxiety, depression, sexual dysfunction, impotence and eating disorders (see, for example, New, Med. Res. Rev., Vol. 10, pp 283-326 (1990)).
The compounds of formula (I) are thus useful for the treatment of various disease states, including those disease states alleviable by treatment with compounds having selective .alpha..sub.2 -adrenoceptor antagonist activity and/or 5-HT.sub.1A receptor partial agonist activity in mammals. Such treatment includes, for example, lowering of blood pressure in normotensive and hypertensive mammals, treatment of disorders of peripheral blood flow, wound healing, inhibition of platelet aggregation, treatment of sexual dysfunction, alleviation of depression, treatment of anxiety, alleviation of male impotence, lowering of intraocular pressure, and palliation of diabetes and its sequelae such as diabetic retinopathy, nephropathy, neuropathy and associated circulatory disturbances. The compounds of formula (I) are particularly useful for the treatment of sexual dysfunction, depression and anxiety.
2. Previous Disclosures
The novel compounds of this invention are various decahydro-8H-isoquino[2,1-g][1,6]naphthyridine and decahydrobenzo[a]pyrrolo[2,3-e]quinolizine derivatives, the compounds of formula (I). Compounds somewhat structurally related are described in U.S. Pat. Nos. 4,454,139, 4,550,114, 4,791,108, 4,886,798, and in Nouveau J. Chim. 4(3), 199-202 (1980).